Prophylactic Treatment of Undernourished Mice with Cotrimoxazole Induces a Different Profile of Dysbiosis with Functional Metabolic Alterations

Cells. 2022 Jul 23;11(15):2278. doi: 10.3390/cells11152278.

Abstract

Childhood malnutrition affects physiology and development. It increases infection rates, which may not present clinical signs in severe cases. The World Health Organization recommends prophylactic treatment with cotrimoxazole (SXT) and nutritional recovery to overcome this issue. This treatment is controversial, since evidence of a reduction in morbidity and mortality is not a consensus and could induce the development of antibiotic-resistant bacteria. Moreover, the impact of using this wide-spectrum antibiotic on gut microbiota in a critical period of development, and weakness is unknown. To understand how SXT prophylaxis could affect gut microbiota in undernutrition, we induced protein-energy undernutrition (PEU) in weaning C57BL/6 mice for three weeks and treated animals with SXT for two weeks. Using 16S rRNA gene sequencing, we compared the taxonomic composition and metabolic pathways of control mice, animals submitted to undernutrition (UND), treated with SXT, or undernourished and SXT treated (UND + SXT). We identified that UND mice had a significant increase in predicted pathways related to metabolic syndromes later in life. The prophylactic SXT treatment alone resulted in a significant loss in community richness and beta diversity. Furthermore, we identified the reduction of three genera in SXT treated mice, including the butyrate producers Faecalibacterium and Anaerotruncus. Both UND and double challenge (UND + SXT) resulted in a reduction of the amino acid's biosynthesis pathway related to cell growth. Our results show that the SXT prophylaxis of young mice during an undernourishment period did not re-establish the undernourished microbiota community composition similar to healthy controls but induced a distinct dysbiotic profile with functional metabolic consequences.

Keywords: cotrimoxazole; dysbiosis; metabolism; microbiome; undernutrition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents
  • Dysbiosis* / microbiology
  • Malnutrition* / complications
  • Malnutrition* / drug therapy
  • Malnutrition* / microbiology
  • Mice
  • Mice, Inbred C57BL
  • RNA, Ribosomal, 16S / genetics
  • Trimethoprim, Sulfamethoxazole Drug Combination

Substances

  • Anti-Bacterial Agents
  • RNA, Ribosomal, 16S
  • Trimethoprim, Sulfamethoxazole Drug Combination

Grants and funding

No direct funding for the execution of this study was received. L.B.E., G.F.G., and I.M.A.M received a CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) student fellowship. O.B.-R. received a CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) research productivity fellowship.